Biomedical subjects
Publications and source records attributed to R Mittal.
A case of reflex sympathetic dystrophy (RSD) after total hip replacement (THR) is reported. It is a very unusual cause of pain after any arthroplasty procedure. Three-phase bone imaging diagnosed the condition and sympathetic blockade was used for confirming and treating the condition. The role of the bone scan in differentiating RSD from other causes of pain after THR is highlighted.
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We present our experience on the comparison of three different modes of steroid therapy, oral prednisolone (OP), intravenous dexamethasone (IVDX) and intravenous methylprednisolone (IVMP) in the treatment of acute rejection (AR) in renal allograft recipients. Between January 1980 and January 1992, 206 patients underwent live related renal transplantation. Before 1990, all received prednisolone (PRED) and azathioprine (AZA) only. After 1990, patients were given PRED, AZA and cyclosporine (CsA). After 1 year, CsA was stopped and patients were converted to a two-drug regimen only. Of the 206 patients, 180 (87.4%) were male and mean age was 30.3+/-8.7 years (range 14-63). During the mean follow-up of 43.5 months, 178 episodes of AR were seen in 121 patients. Each episode was considered as a separate entrant in the study. Conventional immunosuppression was given in 151 episodes and 27 episodes were on triple-drug therapy. Diagnosis of AR was made by clinical, sonography, nuclear scan with or without graft biopsy evidence. Of the 178 AR, 110 (61.8%) were within 3 months, 36 (20.2%) were between 3 months and 1 year and 32 (18%) were after 1 year. OP was given in 11 cases while IVDX and IVMP were given in 48 and 119 cases respectively. Overall, 154 (86%) showed either a complete or partial response to antirejection therapy. Response to therapy was 91, 90 and 85% in OP, IVDX and IVMP groups respectively. There was no statistical difference in response rate in different groups. There was also no difference in side effects in three different groups. Our data suggest that it is the high dose of steroid rather than mode of therapy which is responsible for therapeutic benefit in treatment of AR.
Secondary neoplasms of the heart are more common than primary tumours. Metastasis occurs most commonly from bronchogenic carcinoma followed by lymphoma and carcinoma breast. Most often cardiac metastasis go undetected as they are asymptomatic and occurs as a terminal event. A 51 year old lady who developed cardiac metastasis from carcinoma breast diagnosed during life is reported with brief review of the literature.
The coastal teleost species, Periophthalmus dipes, commonly known as the mudskipper, was exposed to three sublethal concentrations (5, 10 and 15 mg/l) of potassium chromate for three exposure durations (2, 4 and 6 days). The study compares the dose- and duration-dependent effects of Cr(VI), as potassium chromate, on the ATPase systems in various organs of this fish species. In this study, effects of Cr(VI) stress on total ATPase, (Na+,K+)-ATPase, (Ca+2)-ATPase, (Mg+2)-ATPase, (Ca+2, HCO3-)-ATPase and (Mg+2,HCO3-)-ATPase in gills, kidney and intestine were estimated. A general dose- and duration-dependent inhibitory trend was observed. However, it is evident that exposure duration is more important then dose in the inhibition of the activity of the enzymes. At some concentrations, initial stimulation of the activity of some enzymes were also noticed. However, maximum inhibition was observed in higher Cr(VI) concentrations exposed for the longest time. It is possible that this inhibition of the ATPases by Cr(VI) blocked the active transport system of the gill epithelial as well as chloride cells, glomerular and epithelial cells of the tubules and thus altered the osmoregulatory mechanism of the fish. It appears that this heavy metal ion alters the membrane permeability of the intestinal epithelial cells and other layer of cells by altering the activity of ATPases, resulting in a breakdown of the active transport mechanism needed for the absorption of nutrients, ions and metabolites.
Unlike the alpha subunits of heterotrimeric guanosine triphosphate (GTP)-binding proteins, Ras-related GTP-binding proteins have hitherto been considered not to bind or become activated by tetrafluoroaluminate (AIF4-). However, the product of the proto-oncogene ras in its guanosine diphosphate (GDP)-bound form interacted with AIF4 - in the presence of stoichiometric amounts of either of the guanosine triphosphatase (GTPase)-activating proteins (GAPs) p120GAP and neurofibromin. Neither oncogenic Ras nor a GAP mutant without catalytic activity produced such a complex. Together with the finding that the Ras-binding domain of the protein kinase c-Raf, whose binding site on Ras overlaps that of the GAPs, did not induce formation of such a complex, this result suggests that GAP and neurofibromin stabilize the transition state of the GTPase reaction of Ras.
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Glutamic acid-203 of the alpha subunit of transducin (alphaT) resides within a domain that undergoes a guanosine triphosphate (GTP)-induced conformational change that is essential for effector recognition. Changing the glutamic acid to an alanine in bovine alpha(T) yielded an alpha subunit (alpha(T)E203A) that was fully dependent on rhodopsin for GTP-guanosine diphosphate (GDP) exchange and showed GTP hydrolytic activity similar to that measured for wild-type alpha(T). However, unlike the wild-type protein, the GDP-bound form of alpha(T)E203A was constitutively active toward the effector of transducin, the cyclic guanosine monophosphate phosphodiesterase. Thus, the alpha(T)E203A mutant represents a short-circuited protein switch that no longer requires GTP for the activation of the effector target phosphodiesterase.
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The incidence of post-transplant diabetes mellitus (PTDM) was evaluated in 250 patients who underwent live-related renal transplantation at our hospital between 1978 and 1992. Twelve (4.8%) patients developed PTDM requiring drug therapy. PTDM occurred in 4 of 197 (2%) patients on conventional prednisolone-azathioprine immunosuppression as compared to 8 of 53 (15.1%) patients receiving cyclosporine in addition (triple-therapy). Three patients (25%) developed PTDM during or immediately following anti-rejection therapy with intravenous methylprednisolone. Eight patients (66.6%) developed PTDM within six months of transplantation. Majority of our patients (66.6%) could be managed successfully with oral hypoglycemic agents. Two patients (16.6%) showed spontaneous resolution of hyperglycemia within six months of onset of PTDM. Eleven patients (91.6%) were symptomatic for their hyperglycemia with two patients presenting as 'pseudorejection' and one with diabetic ketoacidosis. Females were more predisposed to develop PTDM in our study (10% vs. 4.1%). HLA-B15 and DR 3 were the commonest phenotypes in our PTDM patients. No other known predisposing or triggering factors associated with PTDM were found in our patients. The current study suggests, that addition of cyclosporine to the conventional immunosuppression in live-related renal allograft recipients has contributed to an increased incidence of post-transplant diabetes mellitus. Close and regular blood sugar monitoring is thus recommended in post-transplant patients especially those on triple drug immunosuppression.
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In this work, we have used resonance energy transfer to determine the relative positions of a reactive cysteine residue on the gamma subunit of the retinal cyclic GMP phosphodiesterase (gamma PDE) and a reactive lysine residue on the alpha subunit of transducin (alpha T). The single cysteine residue on gamma PDE (residue 68) is located at a site that is sensitive to the binding of both the inactive and active forms of alpha T. This is demonstrated by the finding that the addition of an alpha T-GDP complex to a gamma PDE subunit labeled with the environmentally-sensitive probe 2-(4-maleimidoanilino)naphthalene-6-sulfonate (MIANS) results in an enhancement in the MIANS fluorescence. The alpha TGDP-induced fluorescence enhancement is dose-dependent and yields an apparent Kd value of approximately 3 microM. Activation of alpha TGDP by aluminum fluoride, when bound to the MIANS-labeled gamma PDE (M-gamma PDE), then results in a quenching of the MIANS fluorescence. The aluminum fluoride-induced change in M-gamma PDE fluorescence occurs on a time scale identical to that observed for changes in the intrinsic alpha T fluorescence that correspond to activating conformational changes in the alpha T "switch II" region. These results suggest that the induction of the activated state of the alpha T subunit results in a change in conformation close to cysteine 68 in gamma PDE.(ABSTRACT TRUNCATED AT 250 WORDS)
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We prospectively monitored clinical data and renal function at monthly intervals in 165 patients who had received living-related-donor renal allografts in our institution between January 1981 and December 1991 and had a functioning allograft for 1 year or longer. During a mean follow-up period of 47.2 (range 13-155) months, 32 patients (17.2%) developed late acute rejections, of which 14 (43.7%) were asymptomatic. Amongst the symptomatic late acute rejections, worsening of hypertension was the commonest finding, being present in 11 (61.1%) patients, followed by oliguria in 8 (44.4%) and weight gain in 7 (38.8%) patients. Of these 32 late acute rejections, as many as 28 (87.5%) showed a response to antirejection therapy with high-dose steroids: 5 (15.6%) a complete response and 23 (71.9%) a partial response. The response rate was 100% if it was the first acute rejection (20% complete and 80% partial), 78.6% if it was the second (14.3% complete and 64.3% partial), and no or only a partial response to treatment if it was the third acute rejection episode. On long-term follow-up, patients who had responded to to antirejection treatment had a significantly better graft survival as compared with nonresponding patients: 76 and 27%, respectively. Our observations suggest that routine monitoring of the renal function at frequent intervals is essential for early diagnosis and treatment of acute rejections, even during the late posttransplant period. The chances of a response to antirejection therapy are higher during the first episode of late acute transplant rejection as compared with second or a third late rejection event.
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We have used resonance energy transfer to read out the interactions of the alpha subunit of transducin (alpha T) with the transducin beta gamma subunit complex (beta gamma T) and to compare the rate of aluminum fluoride-induced alpha T activation, as reflected by the enhancement of the alpha T tryptophan fluorescence, with the rate for the dissociation of holotransducin into its component subunits. Specifically, a beta gamma T complex that was labeled with 5-(iodoacetamido)fluorescein (IAF-beta gamma T) served as a donor for resonance energy transfer and an alpha T-GDP species labeled with eosin 5-isothiocyanate (EITC-alpha TGDP) served as the acceptor. The quenching of IAF-beta gamma T fluorescence emission by the addition of the EITC-alpha TGDP species, due to resonance energy transfer between the IAF and EITC moieities, ranged from 10% to 15%. The association of the transducin subunits was rapid (i.e., within the time period of mixing) and dose-dependent, yielding an apparent Kd of approximately 150 nM for the alpha TGDP/beta gamma T interaction. Unexpectedly, we find that the dissociation of IAF-beta gamma T from an aluminum fluoride-activated alpha TGDP/IAF-beta gamma T complex occurs prior to the onset of the intrinsic fluorescence changes in alpha T that accompany activation of this subunit. Thus, there are at least two structural changes in alpha T that result from the occupation of the gamma-phosphate position in the nucleotide binding cleft of alpha T by aluminum fluoride.(ABSTRACT TRUNCATED AT 250 WORDS)
Human papillomaviruses (HPVs) are etiologically involved in cervical neoplasia, and epidemiological evidence suggests that steroid hormones can increase the risk of this cancer in HPV-infected women. Steroids can interact with hormone-response elements in the viral long control region, enhancing HPV transcription and resulting in transformation of cervical cells. Subsequent malignant progression may involve virus-induced chromosomal instability, facilitating viral DNA integration and deregulation of gene expression.